Date: 14 Nov 1996 19:58:34
From: aidsnews@igc.org
Subject: AIDS Treatment News #259
AIDS TREATMENT NEWS Issue #259, November 15, 1996
phone 800/TREAT-1-2, or 415/255-0588
CONTENTS:
Birmingham UK Drug Therapy Conference -- Early Report
Federal Team Developing Treatment Principles for HIV
Infection
1592: Two Studies Recruiting
The New Antiretroviral Arsenal
Medical Marijuana Wins in California and Arizona
FDA Internet Regulation? Public Comment Accepted until
December 16
AZT Twice-Daily Tablets Approved; Dosing Concerns
Retroviruses Conference: Press Deadline December 6
Qigong Program on San Francisco KQED TV, Beginning December 7
*************************
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***** Birmingham UK Drug Therapy Conference -- Early Report
by John S. James
The important 3rd International Congress on Drug Therapy in
HIV Infection took place in Birmingham, UK, November 3-7; we
could not attend and are still gathering information as we go
to press November 12. There was much interest in studies
relevant to the complete suppression of HIV replication by
drugs.
A small but widely discussed study at the University of
Amsterdam found that antiviral treatment which reduced viral
load to undetectable levels in the blood, also reduced viral
load to undetectable levels in lymph tissue. This was found
in six out of six patients in a substudy of a larger trial.
The lymph tissue was taken by a biopsy of the tonsils (which
is much less invasive than the conventional procedure of
removing a lymph node), before starting treatment and again
after six months of treatment.
Researchers at the University of Minnesota developed the
methodology to measure HIV in lymph tissue from tonsils; see
recent paper by Haase AT, Henry K, Zupancic M and others,
"Quantitative Image Analysis of HIV-1 Infection in Lymphoid
Tissue," SCIENCE, November 8, 1996, pages 985-989.
Undetectable HIV viral load in the lymph nodes does NOT mean
that the virus has been eradicated -- only that it is not
actively reproducing. This viral load test only looks for
viral particles; it does not detect the viral DNA that is
still in the patients' cells -- ready to start up the
infection again if the drugs are stopped. No one knows
whether or not all these cells will eventually be eliminated
by the body, if replication can be stopped for long enough.
While the growth of the virus is being completely suppressed,
drug resistance apparently does not develop. The virus
develops resistance when it is able to reproduce to some
degree in the presence of the drugs, since then the viral
variants which happen to be resistant to those drugs have a
selective advantage, and can replace the more susceptible
virus.
These results are not surprising, as there have long been
indications that if viral replication is being suppressed in
the blood by antiretroviral drugs, it is also suppressed in
the lymph nodes (where there is much more HIV than in the
blood, and where the virus is more important in the
development of disease). And no one would expect the drug
resistance of the virus to increase if the virus is not
reproducing. But it is important to get direct evidence,
since these questions are central to the interpretation of
viral load tests and the management of therapy.
Note: The drug combination used in this University of
Amsterdam study was ritonavir, AZT, and 3TC, in volunteers
who had not used any antiretroviral before. However, there is
nothing special about this particular combination; all
evidence suggests that what is important is reducing the
viral replication essentially to zero and keeping it there,
using whatever drugs can do so for a particular patient.
Similar suppression of replication has also been achieved
with other combinations using a different protease inhibitor
-- or even no protease inhibitor at all.
The main problem now is that some patients are more difficult
to treat -- especially those with more advanced HIV disease,
those who have already developed resistance to existing
antiretrovirals, and those who cannot tolerate the drugs.
This is why the problem of HIV treatment is not solved,
despite the good results in some people. We need continuing
development of better drugs -- with stronger and more durable
antiviral effects, and/or less toxicity, and/or different
resistance profiles than existing treatments, and/or drugs
which may not be superior on the average but do work for some
people when others treatments do not. And then of course
there are still the economic barriers of getting effective
treatments to those who need them.
More work is also needed on measurement of HIV in lymph
tissue, since the most sensitive tests are quite difficult to
do at this time.
There has long been an ongoing debate about the importance of
aiming specifically for complete suppression of viral
replication, vs. being willing to compromise on partial
suppression due to practical concerns of toxicity, cost, and
onerous compliance with regimens of three drugs or more.
Professional opinion now seems to be moving more strongly
toward the importance of complete suppression whenever
antiviral therapy is used, because of the danger that
otherwise the patients' virus will develop resistance to the
drugs one by one, and each drug in turn will be lost for that
person. This probably means that when therapy is begun, it
will usually be with three or more drugs started together
(instead of starting with one or two, then adding other drugs
when the first ones fail); those who have already used
antivirals will need to start or add combinations of at least
two new drugs they have not seen before. What counts is
keeping the viral load essentially at zero, whatever
treatment that requires, because otherwise the virus will
eventually escape the control of the drugs.
Extending and applying these principles to the treatment of
many different patients in different situations, given the
limitations of the drugs available and the practical
limitations imposed by the difficulties of therapy, will be a
central challenge in AIDS medicine for the next several
years.
***** Federal Team Developing Treatment Principles for
HIV Infection
by John S. James
The Office of AIDS Research (OAR) of the U.S. National
Institutes of Health has selected a panel "to make
recommendations regarding initiation of treatment;
suppression of HIV replication; minimizing or preventing
emergence of drug-resistant HIV variants; prolonging
effectiveness of therapy; and addressing the public health
consequences of transmission of multi-drug resistant
variants."
"The panel's activities will involve a series of meetings and
analysis of the most recent available data. The panel is
expected to work over the next several months to develop
these recommendations, which will help health care
practitioners and HIV-infected individuals make informed
decisions about treatment options. It is also anticipated
that the recommendations of this panel will assist public and
private health care payers in providing reimbursement for
essential care for HIV-infected patients."
The "NIH Panel to Define Principles of Therapy of HIV
Infection" has 24 members and is chaired by Charles
Carpenter, M.D., of Providence, Rhode Island; its executive
secretary is Mark Feinberg, M.D., Ph.D., of OAR. There are
two community representatives: Dawn Averitt, of Women's
Information Service & Exchange (WISE) of Atlanta, and Mark
Harrington of Treatment Action Group (TAG) of New York. Three
panelists are from Europe and Australia, with most of the
U.S. members from the East Coast.
The panel's first meeting is November 13 and 14 in
Washington, during which the panelists will hear more than 30
presentations on the current state of scientific knowledge,
focusing mainly on recent information learned too late for
presentation at the Vancouver international conference in
July.
The meeting occurs after this issue of AIDS TREATMENT NEWS
goes to press, and OAR does not plan to issue a report of
this particular meeting (clearly there will be a report from
the panel eventually). But the list of presentations (from
the draft agenda released by OAR) gives an excellent overview
of the state of the science today, of some of the issues
considered most relevant to designing the best possible
treatments for HIV disease. The titles are listed
chronologically from a November 11 draft agenda, but because
of lack of space we did not include the names and
affiliations of the presenters.
Wednesday November 13, 1996:
Session I: Virus and T Cell Population Dynamics in HIV
Infection
* HIV Replication Dynamics: Virus Turnover and Implications
for Antiviral Therapy
* Analysis of Tissue Reservoirs of HIV Infection
* Human T Cell Populations in HIV-Infected and Uninfected
Individuals
* Regenerative Potential of Human T Cell Populations
* Natural History of T Cell Depletion in AIDS
* Maintenance and Loss of T Cell Homeostasis in HIV Infection
* T Cell Replication Senescence in HIV Infection
Session II: The Relationship Between HIV Replication and
Disease Progression
* Performance Characteristics and Variability of the
Quantiplex (bDNA) Assay for Plasma HIV-1 RNA
* Performance Characteristics and Variability of the Amplicor
(RT-PCR) Assay for Plasma HIV-1 RNA
* Primary HIV-1 Infection and the Establishment of the
Replication "Set Point"
* Serum HIV-1 RNA Levels and Progression to AIDS
* Relationship between Plasma and Cellular HIV-1 RNA Levels
and Progression to AIDS
* Population-Based Studies of Plasma HIV-1 RNA Levels
* Plasma HIV-1 RNA Levels Predict Risk of Disease Progression
and Survival
Section III: Relationship between Therapy-Induced Decreases
in HIV-1 Replication and Protection from Disease Progression
* Correlation Between Decline in HIV-1 RNA Levels and
Clinical Outcomes (2 presentations)
* Cross-Study Comparisons of Therapy-Induced Changes in Viral
Load, CD4 T Cell Counts and Clinical Progression
Thursday November 14, 1996:
Session IV: Therapy-Induced Changes in CD4 T Cell Levels and
Recovery of Immunologic Function
* The Magnitude and Limits of Therapy-Induced CD4 Cell
Increases
* Recovery of T Cell Numbers and Function Following Antiviral
Therapy
Session V: Strategies to Delay or Prevent Antiviral Drug
Resistance
* Understanding and Overcoming HIV-1 Antiviral Drug
Resistance
* Combination Antiviral Therapy and Antiviral Drug Resistance
* Detection of Drug-Resistant HIV Variants (2 sessions)
Session VI: Protease Inhibitors Resistance and Cross
Resistance
* HIV-1 Protease Inhibitors Resistance (2 sessions)
Session VII: Combination Antiviral Therapy of Established
HIV-1 Infection
* Combination Therapy of Primary HIV-1 Infection
* Antiviral Therapy of Primary HIV-1 Infection
* Combination Nucleoside Analog Therapy
* Combination Nucleoside Therapy: Recent Experience and
Future Prospects
* Combination Therapy and Non-Nucleoside RT Inhibitors
* Long-Term Suppression of HIV-1 Replication by Combination
Therapy
* Recent Results with Protease Inhibitors
* New Antiviral Therapies (2 presentations)
* Closing Remarks
***** 1592: Two Studies Recruiting
1592U89, usually called 1592, is an experimental nucleoside
analog drug (in the same class as AZT) with much community
interest, for several reasons. First, research has shown that
under some conditions at least, it can produce a 2-log (100
fold) viral reduction with just one drug. Also, it has good
penetration of the blood-brain barrier, suggesting potential
use for treating AIDS-related dementia. And a third reason
for the intense interest is that 1592 is a new possible
treatment for persons who do not have other options.
[Note: On November 12 THE WALL STREET JOURNAL published a
major article on 1592, "Why Isn't Glaxo's New AIDS Drug Ready
Yet," by Michael Waldholz, page B1; it asks why 1592 has been
in research much longer than other new AIDS drugs but is not
expected to be marketed until almost two years from now, and
is not being made available through expanded access for those
with no other treatment options. Activists suspect that the
drug is being delayed to avoid competing with AZT and 3TC;
Glaxo says it did not know until about a year ago how much
more powerful this drug is than others. It is remarkable how
Glaxo's arguments against expanded access resurrect those
that were used years ago against other AIDS drugs, and long
ago abandoned.]
Glaxo Wellcome is now running two preliminary trials of 1592:
Protocol 2003
This trial will test the antiretroviral activity of 1592 in
40 persons nationally who are already using certain approved
nucleoside analog drugs. Forty persons will be enrolled in
this study, and all will receive the same dose of 1592 (300
mg orally twice a day), in combination with other nucleoside
analogs. There is no placebo. In order to enter this study,
volunteers must be at least 13 years old, must have a CD4
count of at least 100, and must have a viral load of at least
30,000.
But there are complex entry criteria based on pre-existing
antiretroviral therapy; for example, anyone who has used a
protease inhibitor, or a non-nucleoside reverse transcriptase
inhibitor (e.g. nevirapine) is ineligible. In order to enter
this study, a person must fit in at least one of the four
following categories:
* At least 12 months of AZT monotherapy;
* At least 6 months of 3TC and 12 months of AZT;
* At least 6 months of ddI monotherapy;
* At least 6 months of d4T and 12 months of AZT.
Anyone who has had other antiretroviral treatments is not
eligible for this trial.
The trial is being run in eight cities; we list the state,
city, study coordinator, institution, and phone number at
each site. For more information, call the contact person
listed:
* California: Greenbrae (Alison Clayton, Marin County
Specialty Clinic, 415/499-7377);
* California: Los Angeles (Scott Brooks, Kraus Medical
Partners, 213/930-2324);
* California: San Francisco (Debbie Hildebrandt, ViRx, Inc.,
415/353-5623 or 415/474-4440);
* Florida: Ft. Lauderdale (Keith Huber, R.N., North Broward
Hospital District, 954/467-3006 ext. 240);
* Florida: Maitland (Neena Griffin, R.N., Central Florida
Research Initiative, 800/868-3483 ext. 3, or 407/647-3960);
* Georgia: Atlanta (Laura Ray, AIDS Research Consortium of
Atlanta, 404/876-2317 ext. 329);
* Kentucky: Lexington (Karen Meekins, R.N., University of
Kentucky Medical Center, 606/323-3933);
* New York: New York (Ann Marshak, Beth Israel Medical
Center, 212/420-4519).
Protocol CNAB3001
This is a 90-patient phase III study for persons with HIV-
associated dementia. Volunteers will be able to continue
their current antiretroviral treatment in most cases, and
will be randomized to receive 1592 or placebo for 12 weeks.
After the 12 weeks, all participants will receive 1592 for 40
weeks. The dose of 1592 used in this study is 600 mg twice a
day.
To be eligible, persons must be between 18 and 65 years old,
and must have been stable on their current antiretroviral
treatment for at least six weeks. There are a number of
exclusion conditions, especially for certain abnormal
laboratory tests, or for certain unrelated illnesses.
For more information, call the contact person at a site which
you could attend:
Baltimore (Tish Nance, 410/955-7464);
Chapel Hill (Wendy Robertson, 919/966-6727);
New York - Columbia University (Ronda Freedman-Clouse, R.N.
212/960-2230);
New York - Mt. Sinai (Jessica Moise, 212/241-0784);
San Diego - (Mary Anne or Mary McCarthy or Dr. Stephen Brown,
619/543-5059);
San Francisco (Dr. Richard Price, 415/206-3208);
St. Louis (Meridith Glicksman, 314/362-9733).
***** The New Antiretroviral Arsenal
by Denny Smith
In less than one year, the options for managing HIV have more
than doubled. The number of drugs approved to treat HIV
infection has risen to nine, with two others now available to
qualifying persons under expanded-access programs. We
prepared this quick guide to help people orient themselves to
the various drugs and their different names; these brief
descriptions could not possibly be complete, and people with
HIV must work with their physicians to be aware of the
different possible side effects, and the other instructions
which are essential for using these treatments correctly.
Generally no anti-HIV drug should be used alone, given the
ease with which HIV develops resistance. Some drug
combinations have been proven more effective--or have fewer
side effects--than others. But much is still unknown about
combination therapy, and most people must experiment
intelligently with different combinations to see what will
keep both their viral load and treatment-related toxicities
as low as possible.
Most clinicians we know are now making treatment
recommendations based on drug tolerance and viral load,
rather than CD4 cell counts. The CD4 count is now used
largely for deciding when to use prophylaxis therapies to
prevent opportunistic infections.
We have listed the reverse transcriptase inhibitors first,
followed by the protease inhibitors, followed by hydroxyurea,
which was originally developed as an oncology drug, but which
may work in a unique manner against HIV. Important note: The
side effects described for each entry below are only the most
common or important ones. Physicians and patients should
always be prepared for other toxicities, which are described
at length in the product inserts available at any pharmacy.
Reverse Transcriptase Inhibitors
These drugs work by inhibiting an enzyme -- reverse
transcriptase -- which the virus needs to replicate.
* AZT, also called zidovudine, is marketed under the brand
name Retrovir(R). AZT has been combined with all other
antiretrovirals and may work especially well in combination
with 3TC, indinavir, nevirapine or delavirdine. AZT is
valuable for treating cognitive problems caused by HIV
because it penetrates the central nervous system better than
most of the other drugs. It can cause headaches and stomach
upset, but these often go away after a couple weeks. Over
extended periods of use, it can cause anemia (low production
of red blood cells), neutropenia (low white cells) and
myopathy (damage to muscle fibers). These problems resolve if
the drug is discontinued. The usual prescription for AZT has
been two capsules (200 mg) taken three times a day, but
Glaxo-Wellcome will soon be offering a 300 mg capsule that
can be taken twice daily. The dose used for treating
cognitive or motor slowing or dementia is twice the regular
dose: 1200 mg a day.
* ddI, also known as didanosine, is sold under the brand name
VIDEX(R). ddI can be combined with any other antiretroviral,
but may work especially well with d4T, nevirapine or
hydroxyurea. However, ddI, ddC, and d4T can each cause
peripheral neuropathy and pancreatitis, so any combination of
these drugs must be carefully monitored. If you experience
abdominal pain or tingling and numbness in your toes or
fingers, stop taking these drugs and call your healthcare
provider; otherwise, long-term damage may result. The usual
prescription for ddI is two tablets (125 or 200 mg, depending
on body weight) taken twice a day on an empty stomach with
water.
* ddC, also called zalcitabine, is sold as HIVID(R). ddC can
be combined with any other antiretroviral, but must be used
cautiously with ddI or d4T, since all three drugs can cause
neuropathy or pancreatitis. If you experience abdominal pain
or tingling and numbness in your toes or fingers, stop taking
these drugs and call your provider; otherwise, long-term
damage may result. The usual prescription for ddC is one
tablet (0.75 mg) taken three times a day.
* d4T, also known as stavudine, is marketed as Zerit(R). d4T
can be combined with most other antiretrovirals and may work
especially well with ddI or nevirapine. However, d4T must be
used cautiously with ddI or ddC, since all three drugs can
cause neuropathy and pancreatitis. If you experience
abdominal pain or tingling and numbness in your toes or
fingers, stop taking these drugs and call your provider;
otherwise, long-term damage may result. The usual
prescription for d4T is one capsule (30 or 40 mg, depending
on body weight) taken twice a day.
* 3TC, also called lamivudine, is marketed as Epivir(R). 3TC
can be combined with any other antiretroviral and may work
especially well with AZT, nevirapine or delavirdine. 3TC may
resensitize HIV to AZT in people whose virus has become
resistant to AZT. It can cause headaches and insomnia in some
people, but these usually go away after a few weeks. The
usual prescription for 3TC is one tablet (150 mg) taken twice
a day.
Non-Nucleoside Reverse Transcriptase Inhibitors
* Nevirapine is sold under the brand name Viramune(R).
Nevirapine can be combined with most other antiretrovirals,
but has not been widely studied in combination with
delavirdine, hydroxyurea or the protease inhibitors. It may
work especially well with AZT, ddI, d4T, or 3TC. Nevirapine
can cause a serious rash, but this may be avoided by starting
with a low dose, one tablet taken once a day for two weeks,
and then doubled to the usual prescription: one tablet (200
mg) twice a day.
* Delavirdine is available only to people with CD4 counts of
300 or less through an expanded-access program run by Upjohn,
which calls the drug Rescriptor(R). An FDA advisory committee
will consider full approval on November 22. Delavirdine can
be combined with most other antiretrovirals, although it has
not been widely studied in combination with nevirapine,
hydroxyurea or the protease inhibitors. It may work
especially well with AZT and 3TC. Like 3TC, delavirdine may
resensitize the virus to AZT in people who have become
resistant to that drug. Like AZT, delavirdine may be useful
for HIV-related cognitive problems because it can penetrate
the central nervous system. And like nevirapine, it can cause
a rash in some people. The prescription for delavirdine is
four pills (400 mg) taken three times a day.
Protease Inhibitors
These drugs target a different enzyme of the virus -- the HIV
protease -- which is essential for HIV to make working copies
of itself. More than with most drugs, it is very important
not to miss doses of the protease inhibitors.
* Indinavir is sold under the brand name Crixivan(R).
Indinavir can be combined with most other reverse
transcriptase inhibitors, but has not been widely studied in
combination with nevirapine or delavirdine, or hydroxyurea or
the other protease inhibitors. It should definitely not be
combined with ritonavir. Indinavir can cause stomach upset,
kidney stones and generalized discomfort, although drinking
plenty of fluids may prevent the kidney stones. It should be
used with caution with certain other medications, so make
sure your provider knows about everything you are taking. The
usual prescription for indinavir is two capsules (800 mg)
taken three times a day on an empty stomach with a large
glass of water. Try not to miss any doses of this drug, or
the virus could quickly become resistant.
* Ritonavir is marketed as Norvir(R). Ritonavir can be
combined with most other antiretrovirals, but has not been
widely studied in combination with nevirapine, delavirdine,
or hydroxyurea. Ritonavir may work especially well with
saquinavir, but only at doses tested in combination trials,
and it should definitely not be combined with indinavir.
There are many other medications that should be used with
caution or not at all with ritonavir, so tell your provider
exactly what you are taking. Ritonavir can cause stomach
upset, generalized discomfort and tingling or numbness around
the mouth. These might by avoided by starting with a low
dose, three capsules taken twice a day with food, and adding
one capsule each dose every couple days until the usual
prescription is tolerated: six capsules (600 mg) taken twice
a day. The capsules should be stored in a refrigerator. Try
not to miss any doses of this drug, or the virus will quickly
become resistant.
* Saquinavir is sold under the brand name Invirase(TM).
Saquinavir can be combined with most other antiretrovirals,
and may work especially well with ritonavir, but only using
the low doses tested in combination trials. It has not been
widely studied with hydroxyurea, nevirapine, delavirdine, or
the other protease inhibitors. It should also be used with
caution with certain other medications, so make sure your
provider knows about everything you are taking. Saquinavir
can cause mild stomach upset and sun sensitivity, but these
are unusual. The usual prescription for saquinavir--unless
combined with ritonavir--is three capsules (600 mg) taken
three times a day with food. The current formulation of
saquinavir is very poorly absorbed, but taking it with
grapefruit juice helps to increase blood concentrations. A
better formulation will probably be available next year. Try
not to miss any doses of saquinavir, or the virus may become
resistant.
* Nelfinavir was developed by Agouron Pharmaceuticals; its
brand name is VIRACEPT(TM). It is available only through an
expanded-access program to people with CD4 counts of 50 or
less who can no longer tolerate or benefit from the other
three protease inhibitors. Nelfinavir can be combined with
most reverse transcriptase inhibitors, although it has not
been studied in combination with delavirdine or nevirapine,
or hydroxyurea. And because it is so recently available, we
do not know anyone who has tried novel combinations with this
drug. The criteria by which it is dispensed essentially
prohibit the combination of nelfinavir with other protease
inhibitors. It can cause stomach upset or headaches in some
people, and should used with caution with certain other
medications. The prescription for nelfinavir is three tablets
(750 mg) taken three times a day with food.
Miscellaneous
* Hydroxyurea is marketed as Hydrea(R) and is used to treat
melanoma, leukemia, ovarian, and head and neck cancers. It
may fight HIV by partially inhibiting a human enzyme, called
ribonucleotide reductase, which HIV needs. Hydroxyurea may
work especially well with ddI. Like AZT, hydroxyurea can
cause anemia and neutropenia, although this is unlikely using
the low dose usually prescribed for HIV: one capsule (500 mg)
daily. Note: While hydroxyurea is an approved drug for
certain cancers, its use with HIV is experimental.
***** Medical Marijuana Wins in California and Arizona
by John S. James
By 55.7% to 44.3%, California voters passed Proposition 215
to allow medical use of marijuana. Arizona voters passed
Proposition 200 by a much larger margin, 65.3% to 34.7%. The
Arizona measure is broader than California's; in addition to
allowing medical marijuana, it may lead to release of persons
already in prison for certain nonviolent offenses. It is much
less well known than the California initiative, because
supporters in Arizona did not want outside help, due to
sensitivity of Arizona voters to interference in their
affairs.
Californians for Medical Rights, the official sponsor of the
'Yes on 215' campaign, is preparing a brochure for patients
and doctors "who need to know what Proposition 215 means to
them. By the same token, we will help to inform people who
are NOT sick as to why Propositions 215 will not apply to
them. We don't want anyone to get the wrong idea about this
new law, and end up putting themselves at risk
unnecessarily." To leave your name and address to receive a
copy of the free brochure, call the Proposition 215 Patient
Information Hotline, 1-888-YES-4-215 (toll free).
No county in California had less than 40% of voters
supporting the medical marijuana measure, according to a
voter survey of over 2,000 voters published the day after the
election (we do not have the final official figures, which
would include absentee ballots and may differ somewhat from
the survey). The highest support was in San Francisco, with
78% of voters interviewed. Los Angeles supported Proposition
215 by 56%. See the SAN FRANCISCO EXAMINER, November 6, page
A-24, for a vote breakdown for all counties, and statewide by
demographics, political beliefs, etc.
Comment
Despite exaggerated statements from both sides suggesting
that California marijuana laws are now unenforceable, we
suspect that the main immediate effect of Proposition 215
will be to create a limited legal defense in court. A state
proposition cannot overrule Federal laws against marijuana
for medical or other use. It will be necessary to build a
national campaign to change Federal laws.
The biggest ultimate impact of these votes may be to open
doors to rational discussion about the war on drugs. And here
it is clear that the country desperately needs other policy
options besides prohibition or official indifference. This
writer has strongly supported Proposition 215, but would
never want to see massive television and billboard promotion
of marijuana. Today with tobacco, companies sanctimoniously
agree to help keep it from children, while knowing full well
that their future centrally depends on getting children and
teenagers to smoke, since few smokers begin as adults --
leading to highly sophisticated, lavishly financed corporate
promotions to children, cleverly designed to stay mostly
under the radar of civil society.
We need a new category between legal and illegal, for
activities where adults are clearly allowed to make their own
decisions, but where public policy is not neutral,
discouraging an activity by other means than by making it a
crime (such as by prohibiting routine or large-scale
promotion). The Supreme Court has made such policies
difficult, by defining advertising as Constitutionally-
protected "speech" -- making it hard to regulate promotion of
products such as alcohol, tobacco, or marijuana, without
first making them a crime and invoking all the deadly baggage
of prohibition, for no public purpose.
The Proposition 215 demographic breakdowns in the EXAMINER
survey are fascinating. Sex made little difference, with
females slightly more supportive of medical marijuana. There
were big differences by race, with Black most supportive of
proposition 215, Asian least supportive, and White in the
middle. By age, support was lowest among voters over 60.
Voters who currently were paid full-time workers were
considerably more supportive than those who were not.
But what may be most important was the breakdown by whether
the voter has children under 18. There was almost no
difference in support -- only a 2% difference, and the survey
had a margin of error of 3%. We would have thought that the
basis of opposition to this proposition would have been
parents worried that their children could get in trouble with
drugs. But that is not what happened.
What, then, IS the basis of the opposition to medical
marijuana, or to this particular initiative? Polls have
repeatedly shown strong support for the right to use
marijuana for legitimate medical needs; in view of this
consistent support, the 55.7% vote in California seems
disappointing. Supporters should ask the 44.3% who voted
against Proposition 215 what was on their minds. Addressing
their objections will be an important part of making this
initiative work well enough to be an effective national
model.
***** FDA Internet Regulation? Public Comment Accepted until
December 16
On October 16 and 17 the FDA held a public meeting, "FDA and
the Internet: Advertising and Promotion of Medical Products,"
near Washington D.C.; several hundred people attended, mostly
from industry (apparently there were no more than two AIDS
community or activist representatives). This meeting has been
widely reported in the press, but these articles did not tell
their readers that anyone can submit written comments until
December 16.
Background about the meeting was published in the Federal
Register, September 16, volume 61, number 180, pages 48707-
48710. That Federal Register notice included the following
summary:
"The Food and Drug Administration (FDA) is announcing a
public meeting to discuss issues related to the promotion of
FDA-regulated medical products on the Internet. FDA is
seeking participation in the public meeting and written
comments from all interested parties, including, but not
limited to, consumers, patient groups, information vendors,
manufacturers of FDA-regulated medical products, and health
care professionals. This meeting and the written comments are
intended to help guide FDA in making policy decisions on the
promotion of biologics, human and animal drugs, and medical
devices on the Internet and the World Wide Web (the Web)."
The meeting was divided into five discussion groups:
Investigational product information; Chatrooms and
newsgroups; Additional regulatory issues; Website links; and
International issues.
A complete transcript of the two-day meeting is available on
the FDA Web page, http://www.fda.gov
How to Submit Comments
"Submit written comments on the questions to the Dockets
Management Branch (DMB) (HFA-305), Food and Drug
Administration, 12420 Parklawn Dr., rm. 1-23, Rockville, MD
20857. After the meeting, a transcript will be available at
DMB (address above) between 9 a.m. and 4 p.m., Monday through
Friday."
We suggest that persons preparing comments examine the
meeting transcript, available either worldwide through the
Web or at the FDA's Rockville office, or at least read the
Federal Register announcement of the meeting, which includes
the FDA's specific questions for each discussion group.
Comment
From what we have heard after the meeting, it seems unlikely
that the FDA will make major attempts to regulate the content
of medical information on the Internet -- but there is no way
to know for sure. We are concerned about a number of issues,
for example:
* Pharmaceutical and other companies may be pressured to
restrict more of their material to medical professionals --
rolling back the movement toward patient empowerment (some
online material is already restricted). Also, requiring
registration as medical professionals could greatly limit
information flow to developing countries, even to medical
professionals, because doctors there would probably not show
up as licensed in the databases in the U.S. or other home
country of the pharmaceutical company.
* Even aside from Internet issues, restriction of information
about experimental drugs has greatly hindered recruitment in
clinical trials. Why will doctors refer patients, if they do
not understand the rationale of the treatment or the trial
(which companies are often afraid to include in their trial
announcements, lest they be accused of promotion)? The main
problem is not in the FDA's intent, nor in the regulations
themselves, but in overreaction by industry personnel who do
not know the system very well, and are overly fearful of
getting their companies, and therefore their own careers, in
trouble. Formal regulations, or even informal standards and
expectations, could inadvertently extend and exacerbate this
problem, unless great care is used.
* The rapidly developing "global village" world has both
advantages and disadvantages; one of the advantages is a kind
of world medicine built on local traditions. There have long
been much greater differences internationally in medical care
(even between seemingly comparable industrialized countries)
than the public realizes. Traditionally, if the medicine of
one's own country does not work for a patient's condition,
that patient is out of luck. But with world medicine, the
locally approved treatments will still be tried first,
because physicians are most familiar with them; but when
local drugs or procedures are unsuccessful, others can be
borrowed from countries which have different approved
protocols, drugs, indications, and diagnostic tests --
increasing the overall chance of a successful outcome. Today,
individual educated patients and activist movements are at
the leading edge of this change; as world medicine develops,
it will need to become more institutionalized in order to
serve more people. But clearly the benefits of world medicine
are seriously threatened either by medical uniformity imposed
everywhere, or by blocking information about drugs and
indications in those countries where they are not approved.
***** AZT Twice-Daily Tablets Approved; Dosing Concerns
by John S. James
On October 25 the FDA approved a 300 mg AZT tablet, intended
for twice-daily dosing. (AZT is commonly taken as 200 mg
three times a day in the U.S.) The new dose is intended to be
more convenient by reducing the three daily doses to two --
hopefully improving patients' compliance with their
physicians' instructions.
There are concerns that twice-daily dosing may not work as
well as giving the same amount of drug at more frequent
intervals, because of the greater variation in blood levels
throughout the day. These concerns are (1) that low trough
levels could allow viral resistance to develop faster, and
(2) that higher peak levels after each dose could increase
side effects. In defense of twice-daily dosing, Glaxo-
Wellcome notes that 250 mg twice daily is the standard AZT
dose in Europe, that most clinical trials using AZT today use
twice-daily dosing, and that no differences in safety or
efficacy was seen in a trial of 320 volunteers which compared
100 mg every four hours vs. 300 mg every 12 hours for 48
weeks (the trial was not powered to find differences in
efficacy, however, and it did not measure viral resistance).
Glaxo also notes that the new dose is only an option, since
the previous formulation remains available, and that trials
to measure the development of viral resistance are now in
progress or being planned.
***** Retroviruses Conference: Press Deadline December 6
by John S. James
The 4th Conference on Retroviruses and Opportunistic
Infections, January 22-26, 1997 at the Sheraton Washington
Hotel in Washington, DC, will probably be the most important
AIDS conference in the U.S. in 1997. The deadline for
"community based newsletters" (most AIDS-related newsletters)
to register as press is December 6. For "all other press,"
(newspaper and TV reporters, freelance writers on assignment,
etc.) the deadline is January 10, and applications will be
processed first come first served. Many industry publications
may not be allowed to register as press in either category.
There is no on-site registration.
The Community Liaison Subcommittee will review and approve
the community press applications, and applicants will be
notified in mid December. This Subcommittee is excellent, but
only has a limited number of slots to approve.
The bottom line is that anyone who wants to attend this
conference needs to start making arrangements as soon as
possible. For more information, obtain the Press Registration
packet from the Retrovirus Conference Secretariat, c/o
Infections Diseases Society of America (IDSA), 703/299-0200,
fax 703/299-0204.
Press rules include no photography, video recording, or
formal interviews in session rooms or the poster hall, and no
photography elsewhere except with prior approval. Audio
recordings are allowed, but not for republication or
rebroadcast.
For those not going, the published abstracts are scheduled to
be available on the Internet on January 22, at
http://www.idsociety.org. The printed abstract book will be
sent two weeks in advance to all registered press.
Comment
As we have noted in previous articles, some of the press
rules for this conference are highly unusual and a major
impediment to rapid, accurate reporting. For almost ten years
we photographed poster presentations and occasional slides at
AIDS conferences without ever being told not to. At the
Vancouver conference we found that a good-quality video
camera was exceptionally useful, both for recording posters
and for recording key slides with the accompanying
discussion. We have taken these pictures only to assure the
accuracy of our own reporting, never for republication.
Traditionally, only FLASH photography in oral sessions has
been banned, for good reason. But at the retroviruses meeting
the cameras will apparently be limited to interviews in the
press room, damaging accurate technical reporting for no
public benefit.
Another major press problem at the Retroviruses conference is
the requirement that mainstream media register in advance. We
do not know of any effective way to communicate this
requirement to those who need to know. Enforcement will mean
that press is turned away, as happened last year. The public
has a legitimate interest in AIDS research, and is more
likely to provide support if it can see the results.
The happenstance dynamics of one major and prestigious
conference must not be allowed to establish a general pattern
of dysfunctional impediments to the communication of AIDS
research information.
***** Qigong Program on San Francisco KQED TV, Beginning
December 7
A course in Qigong (a traditional Chinese therapeutic
exercise) will be presented on public television in the San
Francisco area, starting Saturday December 7, 6:00 a.m. to
6:30 a.m. for four weeks. It will start again on January 4
and repeat for another four weeks.
This course is also available on videotape through the Immune
Enhancement Project in San Francisco, 800/835-6555; all
proceeds from the sale of this tape are contributed to serve
people with HIV. The course grew out of a Qigong class which
meets twice a week in San Francisco; for information about
this class, call Emilio Gonzalez, 415/255-0265, or George
Wedemeyer, 415/661-2080.
Other public broadcasting stations wanting to broadcast this
series can contact Qigong for Health, through the Immune
Enhancement Project at the 800 number above.
***** AIDS TREATMENT NEWS
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Editor and Publisher:
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AIDS TREATMENT NEWS reports on experimental and
standard treatments, especially those available now. We
interview physicians, scientists, other health
professionals, and persons with AIDS or HIV; we also
collect information from meetings and conferences,
medical journals, and computer databases. Long-term
survivors have usually tried many different treatments,
and found combinations which work for them. AIDS
Treatment News does not recommend particular
therapies, but seeks to increase the options available.
Subscription Information: Call 800/TREAT-1-2
Businesses, Institutions, Professionals: $230/year.
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Special discount for persons with financial difficulties:
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Outside North, Central, or South America, add air mail
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ISSN # 1052-4207
Copyright 1996 by John S. James. Permission granted for
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